A state-of-the-art wide-bore multinuclear NMR instrument operating at a magnetic field of 9.4 Tesla is needed for a group of 9 major users from six different departments (Physiology & Biophysics, Pediatrics, Medicine, Biochemistry, Molecular Pharmacology and Developmental Biology & Cancer) and 24 minor users. Of the major users, Dr. Gupta proposes NMR studies of metal ions (Na+, K+, Ca2+, Mg2+) in a variety of isolated cells and tissues. He seeks to understand involvement of metal ions in cellular proliferation, differentiation, volume regulation, and hormonal control of various cellular processes, and to study the derangement of intracellular ionic concentrations in perfused rat liver to study ionic and metabolic changes accompanying liver regeneration. Drs. John Rosen and Frank Schanne will use wide-bore NMR for their studies on the mechanism of lead toxicity, especially its effect on cellular calcium homeostasis in bone cells. Dr. James Scheuer will use multinuclear NMR of perfused rat heart to study vulnerability of the heart to myocardial ischemia, while Dr. Spitzer will exploit phosphorous NMR to examine renal phosphate transport during development. Dr. Fabry will utilize high resolution NMR to study metabolism of malaria parasitized red cell as well as, in combination with surface coils, to study an animal model for sickle cell vaso-occlusion. Dr. Vern Schramm will utilize NMR for elucidating the catalytic mechanism and transition state structures of glycohydrolases and the role of biotin in the pyruvate carboxylase reaction. Dr. Brewer will continue to pursue applications of NMR in the study of glycopeptide and oligosaccharide interactions with concanavalin A. Dr. Atkinson uses l-D as well as 2-D high field proton NMR spectroscopy of elucidation of complex carbohydrate structure on invertase complementation groups mutant in exocytosis. All of the proposed major and minor users will derive significant benefit from the availability of a wide-bore multinuclear NMR instrument.